Optic atrophy 14

Summary

Optic atrophy 14 (MONDO:0957824) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	optic atrophy 14
Mondo ID	MONDO:0957824
OMIM	620550
UMLS	C5882708
MedGen	1851745
GARD	0026882
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › optic nerve disorder › optic atrophy › primary optic atrophy › hereditary optic atrophy › optic atrophy 14

Related subtypes (14): optic atrophy 13 with retinal and foveal abnormalities, optic atrophy 6, optic atrophy 2, Leber hereditary optic neuropathy, optic atrophy 4, autosomal recessive optic atrophy, OPA7 type, optic atrophy 11, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, autosomal dominant optic atrophy, optic atrophy 10 with or without ataxia, intellectual disability, and seizures, optic atrophy 12, optic atrophy 15, optic atrophy 16, ACO2-related optic atrophy with or without extraocular features

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2626805	NM_019008.6(MIEF1):c.718T>A (p.Tyr240Asn)	MIEF1	Pathogenic	no assertion criteria provided
2626806	NM_019008.6(MIEF1):c.436C>T (p.Arg146Trp)	MIEF1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MIEF1	Limited	Autosomal dominant	optic atrophy 14	2

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MIEF1	HGNC:25979	ENSG00000100335	L0R8F8	Mitochondrial ribosome and complex I assembly factor AltMIEF1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MIEF1	Mitochondrial ribosome and complex I assembly factor AltMIEF1	Assembly factor involved in the biogenesis of the mitochondrial-specific ribosomes (mitoribosomes).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MIEF1	Other/Unknown	no		Complex1_LYR_dom, Complex1_LYR_MIEF1-MP, MAB21L/cGLR

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ cell	1
secondary oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MIEF1	288	ubiquitous	marker	sperm, secondary oocyte, male germ cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MIEF1	252

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MIEF1	L0R8F8	37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitochondrial ribosome-associated quality control	1	122.8×	0.008	MIEF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of mitochondrial fusion	1	3370.4×	0.002	MIEF1
positive regulation of mitochondrial translation	1	1123.5×	0.002	MIEF1
mitochondrial fission	1	1053.2×	0.002	MIEF1
mitochondrial large ribosomal subunit assembly	1	991.3×	0.002	MIEF1
positive regulation of mitochondrial fission	1	766.0×	0.002	MIEF1
positive regulation of protein targeting to membrane	1	561.7×	0.002	MIEF1
mitochondrial respiratory chain complex I assembly	1	411.0×	0.002	MIEF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MIEF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MIEF1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MIEF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.